Acute myeloid leukemia (AML) is an aggressive hematological malignancy that gradually develops resistance to current chemotherapy treatments. The available chemotherapy drugs show serious non-specific cytotoxicity to healthy normal cells, resulting in relapse and low survival rates. Natural small molecules with less toxicity and high selectivity for AML are urgently needed. In this study, we confirmed that pyridoxine (vitamin B6) selectively induces monocyte macrophages to undergo programmed cell death in two different modes: caspase-3-dependent apoptosis in U937 cells or GSDME-mediated pyroptosis in THP-1 cells. Further molecular analysis indicated that blocking the caspase pathway could switch the death to MLKL-dependent necroptosis and subsequent extensive inflammatory response. Pyridoxine also delayed the disease progression in a THP-1 leukemia mouse model. In addition, it induced the death of primary AML cells from AML patients by activating caspase-8/3. Overall, our results identify pyridoxine, a low-toxicity natural small molecule, as a potential therapeutic drug for AML treatment.

急性髓细胞性白血病（AML）是一种侵袭性血液恶性肿瘤，逐渐发展为对当前化疗药物的耐药性。可用的化学疗法药物对健康的正常细胞显示出严重的非特异性细胞毒性，导致复发和低存活率。迫切需要对AML具有较低毒性和高选择性的天然小分子。在这项研究中，我们确认吡ido醇（维生素B6）以两种不同方式选择性诱导单核巨噬细胞经历程序性细胞死亡：U937细胞中依赖caspase-3的凋亡或THP-1细胞中GSDME介导的凋亡。进一步的分子分析表明，阻断半胱天冬酶途径可以将死亡切换为MLKL依赖性坏死病和随后的广泛炎症反应。吡rid醇还可以延缓THP-1白血病小鼠模型的疾病进展。此外，它通过激活caspase-8 / 3诱导AML患者的原发性AML细胞死亡。总体而言，我们的结果表明吡pyr醇是一种低毒的天然小分子，可以作为AML治疗的潜在治疗药物。